Macrophage cell membrane-based nanoparticles: a new promising biomimetic platform for targeted delivery and treatment

Abstract

Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.

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     Dou H, Grotepas CB, McMillan JM, Destache CJ, Chaubal M, Werling J, et al. Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroaids. J Immunol. 2009;183(1):661-669.

     Not in our library10.4049/jimmunol.0900274

102. 102.
     Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19 · 2021

     Not checked
103. 103.

     Ivashkiv LB. Epigenetic regulation of macrophage polarization and function. Trends Immunol. 2013;34(5):216-223.

     Not in our library10.1016/j.it.2012.11.001

104. 104.
     Th1/Th2 Paradigm Extended: Macrophage Polarization as an Unappreciated Pathogen-Driven Escape Mechanism? · 2014

     No notice
105. 105.

     Kumar P, Bose PP. Macrophage ghost entrapped amphotericin b: a novel delivery strategy towards experimental visceral leishmaniasis. Drug Deliv Transl Res. 2019;9(1):249-259.

     Not in our library10.1007/s13346-018-00602-1

106. 106.

     Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, et al. Atherosclerosis. Nat Rev Dis Primers. 2019;5(1):56.

     Not in our library10.1038/s41572-019-0106-z

107. 107.

     Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3):341-355.

     Not in our library10.1016/j.cell.2011.04.005

108. 108.

     Foster CA. VCAM-1/alpha 4-integrin adhesion pathway: therapeutic target for allergic inflammatory disorders. J Allergy Clin Immunol. 1996;98(6 Pt 2):S270-S277.

     Not in our library10.1016/s0091-6749(96)70075-1

109. 109.

     Wolf D, Ley K. Immunity and inflammation in atherosclerosis. Circ Res. 2019;124(2):315-327.

     Not in our library10.1161/circresaha.118.313591

110. 110.

     Huang X, Lin C, Luo C, Guo Y, Li J, Wang Y, et al. Fe3O4@M nanoparticles for MRI-targeted detection in the early lesions of atherosclerosis. Nanomedicine. 2021;33:102348.

     Not in our library10.1016/j.nano.2020.102348

111. 111.
     Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications · 2021

     No notice
112. 112.
     Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines · 2020

     No notice
113. 113.

     Ahn JW, Kim JH, Park K. In vitro photodynamic effects of the inclusion nanocomplexes of glucan and chlorin e6 on atherogenic foam cells. Int J Mol Sci. 2020;22:1.

     Not in our library10.3390/ijms22010177

114. 114.

     Tang D, Wang Y, Wijaya A, Liu B, Maruf A, Wang J, et al. ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis. Regen Biomater. 2021;8:4.

     Not in our library10.1093/rb/rbab033

115. 115.

     Li Y, Che J, Chang L, Guo M, Bao X, Mu D, et al. CD47- and integrin α4/β1-comodified-macrophage-membrane-coated nanoparticles enable delivery of colchicine to atherosclerotic plaque. Adv Healthc Mater. 2022;11(4):e2101788.

     Not in our library10.1002/adhm.202101788

116. 116.

     Wu G, Zhang J, Zhao Q, Zhuang W, Ding J, Zhang C, et al. Molecularly engineered macrophage-derived exosomes with inflammation tropism and intrinsic heme biosynthesis for atherosclerosis treatment. Angew Chem. 2020;59(10):4068-4074.

     Not in our library10.1002/anie.201913700

117. 117.

     Zhu FD, Hu YJ, Yu L, Zhou XG, Wu JM, Tang Y, et al. Nanoparticles: a hope for the treatment of inflammation in CNS. Front Pharmacol. 2021;12:683935.

     Not in our library10.3389/fphar.2021.683935

118. 118.

     Langen UH, Ayloo S, Gu C. Development and cell biology of the blood-brain barrier. Annu Rev Cell Dev Biol. 2019;35:591-613.

     Not in our library10.1146/annurev-cellbio-100617-062608

119. 119.
     Functional morphology of the blood–brain barrier in health and disease · 2018

     No notice
120. 120.

     Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13-25.

     Not in our library10.1016/j.nbd.2009.07.030

121. 121.

     Daneman R. The blood-brain barrier in health and disease. Ann Neurol. 2012;72(5):648-672.

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122. 122.

     Samii A, Nutt JG, Ransom BR. Parkinson’s disease. Lancet. 2004;363(9423):1783-1793.

     Not in our library10.1016/s0140-6736(04)16305-8

123. 123.

     Zhao Y, Haney MJ, Mahajan V, Reiner BC, Dunaevsky A, Mosley RL, et al. Active targeted macrophage-mediated delivery of catalase to affected brain regions in models of Parkinson’s disease. J Nanomed Nanotechnol. 2011;S4:003.

     Not in our library10.4172/2157-7439.s4-003

124. 124.

     Batrakova EV, Li S, Reynolds AD, Mosley RL, Bronich TK, Kabanov AV, et al. A macrophage-nanozyme delivery system for Parkinson's disease. Bioconjug Chem. 2007;18(5):1498-1506.

     Not in our library10.1021/bc700184b

125. 125.

     Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18-30.

     Not in our library10.1016/j.jconrel.2015.03.033

126. 126.

     Haney MJ, Suresh P, Zhao Y, Kanmogne GD, Kadiu I, Sokolsky-Papkov M, et al. Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery. Nanomedicine. 2012;7(6):815-833.

     Not in our library10.2217/nnm.11.156

127. 127.

     Han Y, Gao C, Wang H, Sun J, Liang M, Feng Y, et al. Macrophage membrane-coated nanocarriers co-modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer’s disease mice. Bioact Mater. 2021;6(2):529-542.

     Not in our library10.1016/j.bioactmat.2020.08.017

128. 128.

     Caron I, Papa S, Rossi F, Forloni G, Veglianese P. Nanovector-mediated drug delivery for spinal cord injury treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014;6(5):506-515.

     Not in our library10.1002/wnan.1276

129. 129.

     Yanagisawa S, Katoh H, Imai T, Nomura S, Watanabe M. The relationship between inflammasomes and the endoplasmic reticulum stress response in the injured spinal cord. Neurosci Lett. 2019;705:54-59.

     Not in our library10.1016/j.neulet.2019.04.033

130. 130.

     Teng YD, Choi H, Onario RC, Zhu S, Desilets FC, Lan S, et al. Minocycline inhibits contusion-triggered mitochondrial cytochrome C release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci U S A. 2004;101(9):3071-3076.

     Not in our library10.1073/pnas.0306239101

131. 131.

     Xia N, Gao Z, Hu H, Li D, Zhang C, Mei X, et al. Nerve growth factor loaded macrophage-derived nanovesicles for inhibiting neuronal apoptosis after spinal cord injury. J Biomater Appl. 2021;36(2):276-288.

     Not in our library10.1177/08853282211025912

132. 132.

     Tang W, Yang Y, Yang L, Tang M, Chen Y, Li C. Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states. Asian J Pharm Sci. 2021;16(4):459-470.

     Not in our library10.1016/j.ajps.2021.03.005

133. 133.
     Macrophage‐Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke · 2021

     No notice
134. 134.

     Pang L, Zhu Y, Qin J, Zhao W, Wang J. Primary M1 macrophages as multifunctional carrier combined with PLGA nanoparticle delivering anticancer drug for efficient glioma therapy. Drug Deliv. 2018;25(1):1922-1931.

     Not in our library10.1080/10717544.2018.1502839

135. 135.

     Chuang SY, Lin CH, Huang TH, Fang JY. Lipid-based nanoparticles as a potential delivery approach in the treatment of rheumatoid arthritis. Nanomaterials. 2018;8(1):42.

     Not in our library10.3390/nano8010042

136. 136.

     Chen M, Li MH, Zhang N, Sun WW, Wang H, Wang YA, et al. Pro-angiogenic effect of exosomal microRNA-103a in mice with rheumatoid arthritis via the downregulation of hepatocyte nuclear factor 4 alpha and activation of the JAK/STAT3 signaling pathway. J Biol Regul Homeost Agents. 2021;35(2):629-640.

     Not in our library10.23812/20-537-a

137. 137.

     Li H, Feng Y, Zheng X, Jia M, Mei Z, Wang Y, et al. M2-type exosomes nanoparticles for rheumatoid arthritis therapy via macrophage re-polarization. J Control Release. 2022;341:16-30.

     Not in our library10.1016/j.jconrel.2021.11.019

138. 138.

     Fontana F, Albertini S, Correia A, Kemell M, Lindgren R, Makila E, et al. Bioengineered porous silicon nanoparticles@macrophages cell membrane as composite platforms for rheumatoid arthritis. Adv Fun Mater. 2018;28(22):1801355.

     Not in our library10.1002/adfm.201801355

139. 139.

     Li R, He Y, Zhu Y, Jiang L, Zhang S, Qin J, et al. Route to rheumatoid arthritis by macrophage-derived microvesicle-coated nanoparticles. Nano Lett. 2019;19(1):124-134.

     Not in our library10.1021/acs.nanolett.8b03439

140. 140.
     Employing Macrophage-Derived Microvesicle for Kidney-Targeted Delivery of Dexamethasone: An Efficient Therapeutic Strategy against Renal Inflammation and Fibrosis · 2019

     No notice
141. 141.

     Ma Y, Gao W, Zhang Y, Yang M, Yan X, Zhang Y, et al. Biomimetic MOF nanoparticles delivery of C-Dot nanozyme and CRISPR/Cas9 system for site-specific treatment of ulcerative colitis. ACS Appl Mater Interfaces. 2022;14(5):6358-6369.

     Not in our library10.1021/acsami.1c21700

142. 142.

     Zhang Q, Zhou J, Zhou J, Fang RH, Gao W, Zhang L. Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis. Nat Commun. 2021;12(1):4136.

     Not in our library10.1038/s41467-021-24447-4

143. 143.

     Pei W, Li X, Bi R, Zhang X, Zhong M, Yang H, et al. Exosome membrane-modified M2 macrophages targeted nanomedicine: treatment for allergic asthma. J Control Release. 2021;338:253-267.

     Not in our library10.1016/j.jconrel.2021.08.024

144. 144.

     Teo KYW, Sevencan C, Cheow YA, Zhang S, Leong DT, Toh WS. Macrophage polarization as a facile strategy to enhance efficacy of macrophage membrane-coated nanoparticles in osteoarthritis. Small Sci. 2022;2(4):2100116.

     Not in our library10.1002/smsc.202100116

145. 145.

     Hu C, Lei T, Wang Y, Cao J, Yang X, Qin L, et al. Phagocyte-membrane-coated and laser-responsive nanoparticles control primary and metastatic cancer by inducing anti-tumor immunity. Biomaterials. 2020;255:120159.

     Not in our library10.1016/j.biomaterials.2020.120159

146. 146.

     Zhao H, Li L, Zhang J, Zheng C, Ding K, Xiao H, et al. C-C chemokine ligand 2 (CCL2) recruits macrophage-membrane-camouflaged hollow bismuth selenide nanoparticles to facilitate photothermal sensitivity and inhibit lung metastasis of breast cancer. ACS Appl Mater Interfaces. 2018;10(37):31124-31135.

     Not in our library10.1021/acsami.8b11645

147. 147.

     Rao L, He Z, Meng Q-F, Zhou Z, Bu L-L, Guo S-S, et al. Effective cancer targeting and imaging using macrophage membrane-camouflaged upconversion nanoparticles. J Biomed Mater Res Part A. 2017;105(2):521-530.

     Not in our library10.1002/jbm.a.35927

148. 148.

     Bhattacharyya S, Ghosh SS. Transmembrane TNFα-expressed macrophage membrane-coated chitosan nanoparticles as cancer therapeutics. ACS Omega. 2020;5(3):1572-1580.

     Not in our library10.1021/acsomega.9b03531

149. 149.

     Li Y, Yan T, Chang W, Cao C, Deng D. Fabricating an intelligent cell-like nano-prodrug via hierarchical self-assembly based on the DNA skeleton for suppressing lung metastasis of breast cancer. Biomater Sci. 2019;7(9):3652-3661.

     Not in our library10.1039/c9bm00630c

150. 150.

     Rayamajhi S, Nguyen TDT, Marasini R, Aryal S. Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery. Acta Biomater. 2019;94:482-494.

     Not in our library10.1016/j.actbio.2019.05.054

151. 151.

     Fu J, Wang D, Mei D, Zhang H, Wang Z, He B, et al. Macrophage mediated biomimetic delivery system for the treatment of lung metastasis of breast cancer. J Controlled Release. 2015;204:11-19.

     Not in our library10.1016/j.jconrel.2015.01.039

152. 152.

     Haney MJ, Zhao Y, Jin YS, Li SM, Bago JR, Klyachko NL, et al. Macrophage-derived extracellular vesicles as drug delivery systems for triple negative breast cancer (TNBC) therapy. J Neuroimmune Pharmacol. 2020;15(3):487-500.

     Not in our library10.1007/s11481-019-09884-9

153. 153.

     Wayne EC, Long C, Haney MJ, Batrakova EV, Leisner TM, Parise LV, et al. Targeted delivery of sirna lipoplexes to cancer cells using macrophage transient horizontal gene transfer. Adv Sci. 2019;6(21):1900582.

     Not in our library10.1002/advs.201900582

154. 154.

     Nguyen VD, Min H-K, Kim D-H, Kim C-S, Han J, Park J-O, et al. Macrophage-mediated delivery of multifunctional nanotherapeutics for synergistic chemo-photothermal therapy of solid tumors. Appl Mater Interfaces. 2020;12(9):10130-10141.

     Not in our library10.1021/acsami.9b23632

155. 155.

     Zuo W, Chen W, Liu J, Huang S, Chen L, Liu Q, et al. Macrophage-mimic hollow mesoporous fe-based nanocatalysts for self-amplified chemodynamic therapy and metastasis inhibition via tumor microenvironment remodeling. ACS Appl Mater Interfaces. 2022;14(4):5053-5065.

     Not in our library10.1021/acsami.1c22432

156. 156.

     Hou L, Gong X, Yang J, Zhang H, Yang W, Chen X. Hybrid-membrane-decorated prussian blue for effective cancer immunotherapy via tumor-associated macrophages polarization and hypoxia relief. Adv Mater. 2022;34(14):e2200389.

     Not in our library10.1002/adma.202200389

157. 157.

     Evans MA, Huang PJ, Iwamoto Y, Ibsen KN, Chan EM, Hitomi Y, et al. Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial temporal and concentration control. Chem Sci. 2018;9(15):3729-3741.

     Not in our library10.1039/c8sc00015h

158. 158.

     Liu R, An Y, Jia W, Wang Y, Wu Y, Zhen Y, et al. Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer. J Control Release. 2020;321:589-601.

     Not in our library10.1016/j.jconrel.2020.02.043

159. 159.

     Cai JX, Liu JH, Wu JY, Li YJ, Qiu XH, Xu WJ, et al. Hybrid cell membrane-functionalized biomimetic nanoparticles for targeted therapy of osteosarcoma. Int J Nanomed. 2022;17:837-854.

     Not in our library10.2147/ijn.s346685

160. 160.

     Shi M, Shen K, Yang B, Zhang P, Lv K, Qi H, et al. An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection. Theranostics. 2021;11(5):2349-2363.

     Not in our library10.7150/thno.48407

161. 161.

     Cai C, Koch B, Morikawa K, Suda G, Sakamoto N, Rueschenbaum S, et al. Macrophage-derived extracellular vesicles induce long-lasting immunity against hepatitis C virus which is blunted by polyunsaturated fatty acids. Front Immunol. 2018;9:723.

     Not in our library10.3389/fimmu.2018.00723

162. 162.

     Yin C, Zhao Q, Li W, Zhao Z, Wang J, Deng T, et al. Biomimetic anti-inflammatory nano-capsule serves as a cytokine blocker and M2 polarization inducer for bone tissue repair. Acta Biomater. 2020;102:416-426.

     Not in our library10.1016/j.actbio.2019.11.025

163. 163.

     Wu B, Lin L, Zhou F, Wang X. Precise engineering of neutrophil membrane coated with polymeric nanoparticles concurrently absorbing of proinflammatory cytokines and endotoxins for management of sepsis. Bioprocess Biosyst Eng. 2020;43(11):2065-2074.

     Not in our library10.1007/s00449-020-02395-5

164. 164.

     Lee S. Monocytes: a novel drug delivery system targeting atherosclerosis. J Drug Target. 2014;22(2):138-145.

     Not in our library10.3109/1061186x.2013.844158

165. 165.

     Liu B, Yan W, Luo L, Wu S, Wang Y, Zhong Y, et al. Macrophage membrane camouflaged reactive oxygen species responsive nanomedicine for efficiently inhibiting the vascular intimal hyperplasia. J Nanobiotechnol. 2021;19(1):374.

     Not in our library10.1186/s12951-021-01119-5

166. 166.

     Ou Z, Zhong H, Zhang L, Deng M, Zhang W, Wang J, et al. Macrophage membrane-coated nanoparticles alleviate hepatic ischemia-reperfusion injury caused by orthotopic liver transplantation by neutralizing endotoxin. Int J Nanomed. 2020;15:4125-4138.

     Not in our library10.2147/ijn.s253125

167. 167.

     Klyachko NL, Polak R, Haney MJ, Zhao Y, Gomes Neto RJ, Hill MC, et al. Macrophages with cellular backpacks for targeted drug delivery to the brain. Biomaterials. 2017;140:79-87.

     Not in our library10.1016/j.biomaterials.2017.06.017

168. 168.

     Lai J, Deng G, Sun Z, Peng X, Li J, Gong P, et al. Scaffolds biomimicking macrophages for a glioblastoma Nir-Ib imaging guided photothermal therapeutic strategy by crossing blood-brain barrier. Biomaterials. 2019;211:48-56.

     Not in our library10.1016/j.biomaterials.2019.04.026

169. 169.

     Xiao T, He M, Xu F, Fan Y, Jia B, Shen M, et al. Macrophage membrane-camouflaged responsive polymer nanogels enable magnetic resonance imaging-guided chemotherapy/chemodynamic therapy of orthotopic glioma. ACS Nano. 2021;15(12):20377-20390.

     Not in our library10.1021/acsnano.1c08689

170. 170.

     Madsen SJ, Christie C, Hong SJ, Trinidad A, Peng Q, Uzal FA, et al. Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment. Lasers Med Sci. 2015;30(4):1357-1365.

     Not in our library10.1007/s10103-015-1742-5

171. 171.

     Zhang W, Wang M, Tang W, Wen R, Zhou S, Lee C, et al. Nanoparticle-laden macrophages for tumor-tropic drug delivery. Adv Mater. 2018;30(50):e1805557.

     Not in our library10.1002/adma.201805557

172. 172.

     Zhang Z, Li D, Li X, Guo Z, Liu Y, Ma X, et al. PEI-modified macrophage cell membrane-coated PLGA nanoparticles encapsulating dendrobium polysaccharides as a vaccine delivery system for ovalbumin to improve immune responses. Int J Biol Macromol. 2020;165(Pt A):239-248.

     Not in our library10.1016/j.ijbiomac.2020.09.187

173. 173.

     Wu W, Wu D, Yan W, Wang Y, You J, Wan X, et al. Interferon-induced macrophage-derived exosomes mediate antiviral activity against hepatitis B virus through miR-574-5p. J Infect Dis. 2021;223(4):686-698.

     Not in our library10.1093/infdis/jiaa399

Cited by papers we hold 2

• Macrophage-mimetic liposomes co-delivering ceria and Ac2-26 peptide for penumbra protection in ischemic stroke · 2025
  Not checked
• Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets · 2025
  No notice

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